BAC-mediated gene-dosage analysis reveals a role for Zipro1 (Ru49/Zfp38) in progenitor cell proliferation in cerebellum and
skin
Xiangdong W. Yang2, Christopher Wynder2, Martin L. Doughty2
& Nathaniel Heintz1, 2
1
Laboratory of Molecular Biology, Howard Hughes Medical
Institute, The Rockefeller University, 1230 York Avenue, Box
260, New York, New York 10021,
USA.
2
The Rockefeller University, 1230 York
Avenue, Box 260, New York, New York 10021
, USA.
Genetic analysis in mice has most commonly employed two general strategies:
phenotypic screens for spontaneous or induced mutations and genotypic analysis
using homologous recombination or gene trapping to produce deletion or insertion
mutants. Here we use bacterial artificial chromosome (BAC)-mediated gene-dosage
analysis in transgenic mice to reveal novel genetic functions that are not
evident from conventional loss-of-function mutations. We demonstrate a role
for the zinc-finger transcription factor Zipro1 (formerly Ru49
and Zfp38) in the proliferation of granule cell precursors in the developing
cerebellum, and document the contribution of this process to the final stages
of cerebellar morphogenesis. We also show that Zipro1 is expressed
in skin, and increased Zipro1 dosage results in a hair-loss phenotype
associated with increased epithelial cell proliferation and abnormal hair
follicle development.
